Progress in treatment of childhood cancer, once a nearly universally lethal disease, has led to an overall cure rate of nearly 80%. A key component of these advances is the increasing use of a multidisciplinary team approach to treatment. This chapter describes the sequencing of chemotherapy with other treatment modalities such as surgery and radiation therapy and its impact on childhood cancer care. This chapter outlines the advances made by combining chemotherapy with other therapeutic modalities in the predominant solid tumors of childhood, both central nervous system (CNS) (medulloblastoma, ependymoma, glioma, and GCT) and non-CNS (nephroblastoma, neuroblastoma, hepatoblastoma, rhabdomyosarcoma, and noncerebral GCT). In general, the role of chemotherapy is either to reduce tumor volume and maximize the chances of safe surgical resection or to reduce the risk of distant metastases. The timing and type of surgery varies according to the type of tumor as does the timing use of radio and chemotherapy.